Culture

SANTA CRUZ, CA - May 04, 2020 - It's only been three years since UC Santa Cruz researchers proved that long-read human genome assembly using the same nanopore technology developed on campus could be done at all. At the time, it was a monumental effort, requiring 150,000 hours of computing time and weeks of work.

About a year later, using the PromethION nanopore sequencer, a similar effort proved significantly faster, cheaper, and easier, clocking in at about a week. "We sequenced eleven human genomes in nine days, which was unprecedented at the time," said UC Santa Cruz Research Scientist Miten Jain.

Now, researchers at UC Santa Cruz researchers have collaborated on an algorithm designed to accurately and precisely assemble individual, complete human genomes from long-read sequencing data in about six hours and for about $70.

The researchers said they hope their assembler will increase the pace of genomics research and open opportunities. This includes enabling pangenome research to represent the true scale of human diversity, a decidedly more practical pursuit.

Until recently, genomic research has relied exclusively on the reference genome from a single individual selected to represent an entire species. To reflect true human diversity, UC Santa Cruz has embarked on a pangenomic initiative to sequence 350 new, individual human genomes.

As a part of this work, UC Santa Cruz Genomics Institute researchers developed a nanopore long-read sequencing protocol that consistently yields ~60X coverage (~200 gigabases) of a human genome at unprecedented lengths (median read N50 of 42 kb) using three PromethION flow cells. Additionally, ~7X coverage of the genome is in reads exceeding 100 kb in length. This method is highly scalable, both in terms of cost and the number of genomes that can be processed simultaneously. We are now improving this method for higher read lengths and throughput, which will further facilitate our goal of achieving complete, phased, reference-quality genomes.

This large inflow of data necessitated the development of highly efficient software tools, starting with an assembler. "Our new assembler was designed to be cheap and quick, with the goal to be on the cloud," said UC Santa Cruz's Benedict Paten. "It gives us the power to scale nanopore sequencing. Now, I'm confident that we'll be easily assembling hundreds of de novo genomes in the next couple of years."

An extensive team of researchers and developers that was led by Paolo Carnevali from the Chan Zuckerberg Initiative (CZI) -- and included many at the Computational Genomics Lab at the UC Santa Cruz Genomics Institute -- contributed to this solution.

"When I saw the Jain 2018 paper, I was impressed and realized that I could contribute to the computational side of this line of investigation," said Paolo Carnevali. "I had recently met Benedict Paten and decided I wanted to work with his team at UCSC.

The team were soon collaborating. Within months, they had developed and tested the special algorithmic sauce, which they called Shasta.

Shasta is an in-memory computing-driven algorithm that can now help complete a de novo (new, never before processed) human genome assembly in under six hours, the authors say, for an average cost of $70 per sample.

In their paper, "Nanopore sequencing and the Shasta toolkit enable efficient de novo assembly of eleven human genomes," published today in Nature Biotechnology, they describe how Shasta not only yields comparable or better accuracy as its contemporaries but also has the lowest number of misassemblies.

Not satisfied with this milestone, the team saw an opportunity to improve the draft assembly at an affordable cost and turn-around time. "To improve the base-level quality of the assemblies, we used a sequence polisher based on a deep neural network as the final assembly step," explained lead author Kishwar Shafin. "This brought the total cost of the assembly process to less than $200 and 37 hours -- which further reduced the computational overhead of generating long-read assemblies dramatically -- by a factor of five."

The researchers assessed the precision and then validated the accuracy, and noted that they had achieved 99.9% accurate assembly using only nanopore data, a first for the human genome. Further, they generated chromosome-level scaffolds for these polished assemblies using HiC sequencing data.

Research scientist and co-author Karen Miga, who is directing the Data Production Center at UCSC for the Human Pangenome Project, points out the significance of the team's achievements in improved accuracy. "Our aim is not only to expand the diversity of the reference genome but also to resolve the hundreds of gaps that persist across the genome," Miga explains. "Now that we can routinely include these uncharted regions, we have a truly complete assembly of a human genome, and we can begin to explore variations of unknown consequence."

A "step-change" in conservation is needed in order to help save species from extinction in the future, according to an academic at the University of East Anglia (UEA).

Professor of evolutionary genetics Cock van Oosterhout calls for the smart use of genomic data to make populations more resilient to future genetic drift and inbreeding, and proposes a new 'road map' for what needs to be done in conservation to achieve this.

Decades of work by conservation geneticists and international treaties such as the UN Convention on Biological Diversity have attempted to improve the status of biodiversity and maintain genetic diversity across the various forms of life on Earth.

However, according to the most recent global assessment report in 2019, the decline in biodiversity is only accelerating, and one million species are threatened with extinction. The Red List of the International Union for Conservation of Nature (IUCN) also shows that 44.3% of species are currently in decline.

Contributing to this, recent fires in the Amazon and Australia have transformed vast swathes of habitat, climate change places additional pressures on populations, and globally, approximately 75% of the infrastructure planned for 2050 has yet to be built.

Writing in the journal Nature Ecology & Evolution, Prof van Oosterhout, of UEA's School of Environmental Sciences, warns that more needs to be done than just minimizing the loss of biodiversity and genetic variation.

Over the last half century, conservation geneticists have analysed genetic variation and focused on maintaining this in threatened species. While this is important, Prof van Oosterhout says they have ignored an essential part of the genome that is devoid of variation, identical across different species. These are the DNA nucleotides that have been conserved over millions of years of evolution.

These parts of the genome are under strong selection and if mutations occur in these so-called 'ultra-conserved elements', they are bad for the fitness of individuals. When a population declines these mutations become exposed by inbreeding, so the already struggling population is even more at risk.

However, genomics can reveal the presence of this 'mutation load' at the molecular level using tools developed for humans and model animals, such as mice and rats.

Prof van Oosterhout said: "Given that these studies all examine the same ultra-conserved elements, the mutation load can be directly compared between species. Hence, the analyses developed in human genomics could be universally applied across the tree of life, making them very promising tools for conservation genomics.

"We now know the DNA sequences of these ultra-conserved regions in the genomes of threatened species. This means that we can also identify the bad mutations when we sequence these individuals. This has become relatively cheap and it is quick."

Conservation genomics could also help to improve captive breeding in zoos. Rather than just minimising the rate of inbreeding, studbook holders could use the mutation load data of individuals to take on the role of natural selection in the zoo environment.

"With that data and knowledge of which DNA sequences to look out for, we can select against these bad mutations even before they become 'exposed' by inbreeding," said Prof van Oosterhout.

"This would help to prevent - or even turn-back - the deterioration of genepool of the often small zoo populations. Data on the mutation load could also be used to reduce the risk of inadvertently reintroducing harmful mutations into the wild during genetic rescue. Such genomics-informed conservation would make populations more resilient to genetic drift and inbreeding yet to come."

In his paper, Prof van Oosterhout suggests a method that avoids losing valuable genetic variation, an inevitable consequence of selection. It involves selecting the best two offspring of all breeding pairs, so the two with the lowest number of bad mutations. This will reduce the mutation load, maintains the useful genetic variation, and would make the zoo population, and the species, more resilient against current and future inbreeding.

Prof van Oosterhout cautions that there is still work to do to make these genomic approaches reliable, practical tools for conservation. "We still don't know how the mutation load affects the fitness of individuals in the natural environment," he said. "Translating this genomic data into metrics that are relevant to conservation is therefore urgently needed."

"Fortunately, with thousands of genomes currently being sequenced by consortiums, data is rapidly being generated. Together with the rich sample archives that have been collected for some of our threatened species over decades, such as the pink pigeon and the echo parakeet, this would help to translate genomic data into information that is relevant for conservation, for example around the fitness of individuals in their natural environment, and the viability of their populations.

"We should be able to rank individuals, and species, according to their mutation load and relative levels of inbreeding, thereby improving the Red List of animals currently in decline."

Millions more people across the EU could have contracted COVID-19 had strict international travel bans not been implemented, shows a new report by computer modelling experts at Stanford University.

Using a newly developed mathematical epidemiology simulation, the study, published in Computer Methods in Biomechanics and Biomedical Engineering, predicts the huge impact that limiting air travel across the 27 EU nations had on restricting the spread of the disease.

The simulation can show live estimated figures for the growth of spread for each country if we were to remove travel bans today. The images above show how 0.2% of some populations could have become infected by 20th April (when the study was written, 5 April), however these figures change daily.

This new model could now play a vital part in establishing politicians' exit strategies, with the team able to virtually lift travel restrictions between individual communities, states, or countries, to explore the potential gradual changes in spreading patterns and outbreak dynamics.

"There is a well-reasoned fear that easing of current (travel restriction) measures, even slightly, could trigger a new outbreak and accelerate the spread to an unmanageable degree," lead author Ellen Kuhl, Professor of Mechanical Engineering at Standford University comments.

"Global network mobility models, combined with local epidemiology models, can provide valuable insight into different exit strategies. Our results demonstrate that mathematical modelling can provide guidelines for political decision making with the ultimate goal to gradually return to normal while keeping the rate of new COVID-19 infections steady and manageable," says Kevin Linka, lead author and postdoctoral researcher in Dr. Kuhl's group.

From its European origin in Italy, the novel coronavirus spread rapidly via the strongest network connections to Germany, Spain, and France, while slowly reaching the less connected countries, Estonia, Slovakia, and Slovenia.

Currently the levels of population known to be infected with the disease varies from country to country, however as of April 18, with flight being reduced by 89% in Germany, 93% in France, 94% in Italy, and 95% in Spain (Eurostat 2020), the graphs in this study show how the spread has been contained.

"Strikingly, our results suggest that the emerging pattern of the COVID-19 outbreak closely followed global mobility patterns of air passenger travel," confirms Professor Kuhl, whose model can also predict the emerging global diffusion pattern of a pandemic at the early stages of the outbreak.

"Our results suggest that an unconstrained mobility would have significantly accelerated the spreading of COVID-19, especially in Central Europe, Spain, and France."

Unfortunately, the model also confirms how travel bans were introduced too late to stop the Europe-wide outbreak altogether.

"A recent study based on a global metapopulation disease transmission model for the COVID-19 outbreak in China has shown that the Wuhan travel ban essentially came too late, at a point where most Chinese cities had already received many infected travellers (Chinazzi et al. 2020). Our study shows a similar trend for Europe, where travel restrictions were only implemented a week after every country had reported cases of COVID-19 (European Centre for Disease Prevention and Control 2020).

"As a natural consequence, unfortunately, no European country was protected from the outbreak," Professor Kuhl, who is the Robert Bosch Chair of Mechanical Engineering at Standford added.

The first official case of COVID-19 in Europe was reported in France on January 24, 2020, followed by Germany and Finland only three and five days later. Within only six weeks, all 27 countries of the European Union were affected, with the last cases reported in Malta, Bulgaria, and Cyprus on March 9, 2020. At this point, there were 13,944 active cases within the European Union and the number of active cases doubled every three to four days (European Centre for Disease Prevention and Control 2020).

Dr Kuhl adds that although air travel is certainly not the only determinant of the outbreak dynamics, their findings indicate that "mobility is a strong contributor to the global spreading of COVID-19". This is becoming especially important now that many countries are beginning to lift their travel restrictions in an attempt to gradually return to normal.

Other limitations highlighted - like any infectious disease model - include the simulation being subject to data uncertainties from differences in testing, inconsistent diagnostics, incomplete counting, and delayed reporting across all countries.

When cyclones and other natural disasters strike a city or town, the social and economic impacts locally can be devastating. But these events also have ripple effects that can be felt in distant cities and regions -- even globally -- due to the interconnectedness of the world's urban trade networks.

In fact, a new study by researchers at the Yale School of Forestry & Environmental Studies finds that local economic impacts -- such as damage to factories and production facilities -- can trigger secondary impacts across the city's production and trade network. For the largest storms, they report, these impacts can account for as much as three-fourths of the total damage.

According to their findings, published in the journal Nature Sustainability, the extent of these secondary costs depends more on the structure of the production and supply networks for a particular city than on its geographic location. Regional cities that are dependent on their urban network for industrial supplies -- and that have access to relatively few suppliers-- are most vulnerable to these secondary impacts. Larger, global cities such as New York and Beijing, meanwhile, are more insulated from risks.

"Cities are strongly connected by flows of people, of energy, and ideas -- but also by the flows of trade and materials," said Chris Shughrue '18 Ph.D., lead author of the study which is based on his dissertation work at Yale. He is now a data scientist at StreetCred Labs in New York. "These connections have implications for vulnerability, particularly as we anticipate cyclones and other natural hazards to become more intense and frequent as a result of climate change over the coming decades."

The paper was co-authored by Karen Seto, a professor of geography and urbanization science at F&ES, and B.T. Werner, a professor from the Scripps Institution of Oceanography.

"This study is especially important in the context of climate impacts on urban areas," Seto said. "Whereas we tend to consider a city's vulnerability to climate change as limited to local events, this study shows that we need to rethink this conceptualization. It shows that disasters have a domino effect through urban networks."

Using a simulation coupled with a global urban trade network model -- which maps the interdependencies of cities worldwide -- the researchers show how simulated disasters in one location can trigger a catastrophic domino effect.

The global spread of damage was particularly acute when cyclones occurred in cities of North America and East Asia, largely because of their outsize role in global trade networks -- as purchasers and suppliers, respectively -- and because these regions are particularly susceptible to cyclone events.

Often, adverse impacts are primarily caused by a spike in material prices, followed by production losses to purchasers. These production losses eventually can cause industrial shortages, which can then induce additional cycles of price spikes and shortages throughout the production chain.

Similar outcomes have been borne out following real world disasters. For instance, when catastrophic flooding occurred in Queensland, Australia, the impact on coking coal production prompted a 25-percent spike in the global costs. And the economic impacts of Hurricane Katrina extended far beyond New Orleans for several years after the historic storm.

While the example of cyclones can act as a proxy for other isolated disasters -- such as the 2011 tsunami in Japan which caused global economic disruptions, particularly in the auto sector -- the researchers say the findings are particularly relevant in terms of climate-related natural events.

"To be resilient to climate change is not only about building dikes and sea walls, but understanding a city's supply chains and how they are linked to other cities that may be vulnerable," Seto said.

Following the recent Coronavirus outbreak, almost three million people have been infected worldwide, whereas the death toll has already passed the 200,000 mark, according to official reports. Meanwhile, a vaccine remains to be found, and classic medications show low efficacy. Under these conditions, it is up to pharmacologists to do their best in the search of novel treatments. However, laboratory studies are limited by the absence of COVID-19 animal models.

Russian scientists from the Institute of Gene Biology of the Russian Academy of Sciences, the State Virology and Biotechnology Research Center "Vector" and Belgorod University are already working on the development of SARS-CoV-2-sensitive mice to be used as a murine model in tests of potential COVID-19 vaccines and drugs, reports the Office of the Chief State Sanitary Inspector.

To create such a line of mice, researchers have formulated a two-step concept, recently described in the open-access, peer-reviewed scholarly journal Research Results and Pharmacology. Firstly, the mice are to be made biologically safe for routine laboratory practice. Secondly, in order for the mice to be efficient for non-clinical trials, they will need to experience symptoms and pathogenesis as human-like as possible. The scientists believe that they have everything necessary to implement this conception and expect the first results as early as June 2020.

"SARS-CoV-2-inoculated mice will have a human-like pathogenesis and symptoms of the COVID-19. The key difference between a new model and the existing ones will be its biological safety - animals will become sensitive to SARS-CoV-2 only after activation in conditions of a virological laboratory. It makes it possible to nullify the contagion risk for the staff working in nurseries and non-specialised laboratories during a pandemic," the team explains.

Already available data shows that there are two key proteins in the human cells, which are involved in the virus entry. First of all, it is the angiotensin-converting enzyme 2 (ACE2), which is the direct and main target of the coronavirus' "corona". Three lines of transgenic mice with the human ACE2 variant have been found to be susceptible to the SARS-CoV, a causative agent of the SARS outbreak in 2003. However, it was shown that, in addition to ACE2, a molecular pathway of coronavirus invasion contains another important link: the enzyme transmembrane protease serine 2 (TMPRSS2). The blocking of TMPRSS2 prevents SARS-CoV-2 entry on the cell culture in vitro.

To obtain mice with human-like COVID-19 symptoms and pathology, the researchers will introduce human ACE2 and TMPRSS2 genes into the murine genome under the mice's own Tmprss2 promoter. Another key decision on the way of creating the new model is to ensure that SARS-CoV-2 sensitivity is inducible only after the introduction of LoxP sites in front of the human ACE2 and TMPRSS2 genes. As a result, human genes in a murine genome will turn on once a crossbreeding with mice expressing Cre-recombinase occurs.

"The main trick here is that this crossbreed will only happen in specialised virological laboratories, which will prevent the novel line of mice from becoming an infection 'reservoir' in ordinary laboratories," say the researchers.

A study to help determine the rate of novel coronavirus infection in children and their family members in the United States has begun enrolling participants. The study, called Human Epidemiology and Response to SARS-CoV-2 (HEROS), also will help determine what percentage of children infected with SARS-CoV-2, the virus that causes COVID-19, develop symptoms of the disease. In addition, the HEROS study will examine whether rates of SARS-CoV-2 infection differ between children who have asthma or other allergic conditions and children who do not. The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, is sponsoring and funding the HEROS study.

"One interesting feature of this novel coronavirus pandemic is that very few children have become sick with COVID-19 compared to adults," said NIAID Director Anthony S. Fauci, M.D. "Is this because children are resistant to infection with SARS-CoV-2, or because they are infected but do not develop symptoms? The HEROS study will help us begin to answer these and other key questions."

The HEROS study team will rapidly enroll 6,000 people from 2,000 U.S. families already participating in NIH-funded pediatric research studies in 11 cities. Study participants will include both healthy children and children with asthma or other allergic conditions. The study team will prospectively follow these children and their families for six months to determine who gets infected with SARS-CoV-2, whether the virus is transmitted to other family members, and which family members with the virus develop COVID-19.

Leading the HEROS study is Tina V. Hartert, M.D., M.P.H. Dr. Hartert is director of the Center for Asthma and Environmental Sciences Research, vice president for translational research, the Lulu H. Owen Chair in Medicine and a professor of medicine at the Vanderbilt University School of Medicine in Nashville.

"So far, data on the extent of SARS-CoV-2 infection in the U.S. population have been limited to people who physically interact with the healthcare system: those who are tested?especially those who test positive?and those with severe disease," said Dr. Hartert. "These data provide real-time guidance in a setting of limited test availability, but they don't enable us to understand the full extent of SARS-CoV-2 infection in the entire population. The HEROS study will help fill this knowledge gap and inform public health interventions."

Preliminary evidence suggests that having an allergic condition paradoxically may reduce a person's susceptibility to SARS-CoV-2 infection and severe COVID-19 disease. A NIAID-funded study recently examined upper and lower airway cells for the expression of ACE2, the gene that codes for the receptor that the coronavirus uses to infect cells. ACE2 expression is necessary for a cell to make this receptor, but additional steps also are involved. In both children and adults, respiratory allergy, asthma and controlled allergen exposure were associated with significantly reduced ACE2 expression. The expression of ACE2 was lowest in people with high levels of both asthma and sensitivity to allergens.

The HEROS study will further clarify whether reduced ACE2 gene expression in airway cells of children with allergic diseases correlates with a lower rate of SARS-CoV-2 infection and COVID-19.

The study will be conducted completely remotely. Every two weeks, a caregiver in participating families will collect nasal swabs from the child who is the primary study participant and all other family members who are enrolled in the study, and will mail the samples to a laboratory for analysis. On the same day as the nasal swab, the caregiver will complete online questionnaires about each participant's current symptoms, social distancing practices, recent activities outside the home, and recent exposure to people who are sick.

In addition, if any member of the household develops symptoms of a viral illness, the caregiver will fill out another online questionnaire designed to determine the likelihood that the illness is COVID-19. If COVID-19 is likely, the caregiver will collect nasal swabs from all study participants and a stool sample from the symptomatic participant within 24 hours.

Laboratory analyses of nasal swabs will test for SARS-CoV-2 and assess gene expression in the collected airway-surface cells. Investigators hope that these gene expression studies will reveal patterns that correlate with higher or lower risk of infection, COVID-19 symptom development and SARS-CoV-2 transmission.

A caregiver also will collect a blood sample from each study participant two weeks, 18 weeks and 24 weeks after enrollment as well as three weeks after the family's first likely case of COVID-19, if there is one. The blood will be collected using a new, nearly painless device that extracts a small quantity of blood through the surface of the skin. The blood will be analyzed for antibodies to SARS-CoV-2 once an appropriate antibody test becomes available.

Using high-resolution mass spectrometry, researchers have mapped glycan-processing states of the spike protein complex that allows the SARS-CoV-2 virus to infect human cells - finding that SARS-CoV-2 S glycans differ from typical host glycan processing, which may have implications in vaccine design. As scientists seek to combat the virus that causes COVID-19, the development of vaccines has focused on the spike, a protein complex composed of three protomers that protrudes from the virus and binds to the ACE2 receptor on the surfaces of human cells. Each protomer harbors 22 chemical sites that can undergo glycosylation, a biochemical reaction that adds a glycan compound to a protein. How these sites are glycosylated may affect which cells the virus can infect. The same processes could also shield some regions on the spike from being neutralized by antibodies. Seeking insight, Yasunori Watanabe et al. expressed and purified recombinant glycosylated spike complexes, then used enzymes to cut them into peptides each containing a single glycan but representing all glycan sites. The researchers then used a technique called mass spectrometry to determine the glycan composition at each site. They report that the SARS-CoV-2 S protein is less densely glycosylated than some other viral glycoproteins, possessing a sparse "glycan shield," which may be beneficial for the elicitation of potent neutralizing antibodies. Their analysis provides a benchmark that can be used to measure the quality of the spike antigen as researchers develop new vaccines and antibody tests.

Ethanol has five times higher volumetric energy density (6.7 kWh/L) than hydrogen (1.3 kWh/L) and can be used safely in fuel cells for power generation. In Brazil in particular there is great interest in better fuel cells for ethanol as all the country distributes low-cost ethanol produced in a renewable way from sugar cane. Theoretically, the efficiency of an ethanol fuel cell should be 96 percent, but in practice at the highest power density it is only 30 percent, due to a variety of reasons. So there is great room for improvements.

Nafion with nanoparticles

A team led by Dr. Bruno Matos from the Brazilian research institute IPEN is therefore investigating novel composite membranes for direct ethanol fuel cells. A promising solution is tailoring new polymer-based composite electrolyte materials to replace the state-of-the-art polymer electrolyte such as Nafion. Matos and his team use melt extrusion process to produce composite membranes based on Nafion with additional titanate nanoparticles, which have been functionalized with sulfonic acid groups.

Infrared experiments at BESSY II

Matos' team has now thoroughly analysed four different compositions of Nafion composite membranes at the infrared beamline IRIS at BESSY II. Small-angle X-ray scattering measurements confirmed that the titanium particles were synergistically interacting with the ionomer matrix of Nafion.

Proton conductivity increased

Using infrared spectroscopy, they observed that chemical bridges were formed between the sulfonic acid groups of the functionalized nanoparticles. In addition, by following the proton motion along the ionic clusters, they found increased proton conductivity in the composite membrane, even at high concentrations of nanoparticles. "This was a real surprise that we didn't expect," Dr. Ljiljana Puskar, HZB-scientist at the IRIS-Beamline says. The reduction of the conductivity with the increment of the nanoparticles is one of the main hurdles delaying the development of high-performance composite materials. The higher proton conductivity could allow better charge carrier mobility and thus increase the efficiency of the direct ethanol fuel cell.

Advantage of melt extrusion

"This composite membrane can be produced by melt extrusion, which would allow their production on industrial scale," Matos points out.

KINGSTON, R.I. - May 4, 2020 - A team of fisheries scientists and marine policy experts, led by a University of Rhode Island researcher, examined how climate change is affecting the ocean environment and found that the changing conditions will likely result in increased fisheries-related conflicts and create new challenges in the management of global fisheries.

The team's research was published last month in the journal Marine Policy.

Elizabeth Mendenhall, URI assistant professor of marine affairs, said that ocean warming, acidification and sea level rise that are a direct result of climate change are causing populations of fish to shift, making fish increasingly scarce, shifting the boundaries of where nations can legally fish, and increasing the intensity of fishing pressure around the world. The result will be growing conflicts between individual fishermen, fishing communities, fishing nations and fishery managers.

"These conflicts exist at multiple scales," said Mendenhall, who is writing a book about geopolitics and ocean governance. "Some of it is one boat versus another, sometimes it's one country versus another, and it can get very complicated. It isn't just about overfishing any more. There are other drivers and other dynamics involved."

As warming temperatures shift fish populations to different areas, for instance, the bulk of those stocks may cross the borders of a nations' 200-mile exclusive economic zone, making it illegal for those who have fished those stocks for many years to pursue them any longer.

"We're seeing examples of fishermen crossing borders more often now because the stocks they feel they have a right to have shifted across the border," Mendenhall said.

Among the more challenging questions that climate change is raising for fishing nations is what happens when sea level rise submerges an island. Does that change the nation's maritime boundaries?

"It's an ongoing debate about whether you keep your maritime claim even though you have no land base to manage it from," said Mendenhall. "Or does your claim go away? There are a lot of nations that fish over long distances that are ready to exploit those areas if national boundaries no longer exist."

The tiny Japanese atoll of Okinotorishima is one such case. Located in the southernmost archipelago of Japan, its submergence is raising questions about whether Taiwan and China may legally fish in the area claimed by Japan.

"I argue that as sea level rises, Japan's argument gets weaker," said Mendenhall, noting that the countries have not challenged the boundaries based on the island's submergence yet. "The rules on where you can make your maritime claim are based on where the land is.

"The same problem applies to coastlines," she added. "Low-lying countries like Bangladesh and Vietnam could lose a lot of maritime territory as sea level rises. The outer edge of their claim could move closer to their coastline."

The research team makes a series of recommendations based on its findings designed to improve global fishery management. They recommend greater multilateral fishery monitoring, similar to what is in place off East Africa to combat piracy, which can help deter or catch illegal fishers, thereby reducing the chance that individual fishing boats will take matters into their own hands.

"We also suggest that marine protected areas be used, but it's critical that the area protected is one where habitats are still thriving despite climate change," Mendenhall said. "There is concern, however, that when you protect one area, it may displace the fishers to somewhere else and make the problem worse elsewhere. We need to think about the dynamics that protected areas may cause and account for that in the site selection process."

Finally, the researchers recommend strengthening the global fisheries management regime by taking into account climate change and the new sources of fishery conflict. The management boundaries of many fish stocks were drawn decades ago, and some parts of the open ocean are not managed at all because no productive fish stocks were there many years ago, yet there may be fish stocks there in the future. Most importantly, they suggest that the regional fishery management organizations work together to develop coordinated governance systems to better manage fisheries as environmental conditions change and greater conflicts arise.

"These changes to how [regional fishery management organizations] manage fisheries, and how they coordinate and cooperate with one another, can make high seas fisheries management more resilient to shifts in stocks and users, and changes in relative abundance," the researchers conclude.

Washington, DC, May 4, 2020 - Youth who report one of the seven chronic medical conditions (CMCs), including asthma, congenital heart disease, diabetes, epilepsy, inflammatory bowel disease, juvenile idiopathic arthritis, and sickle cell disease, are often diagnosed with an anxiety disorder. A new systematic review in the Journal of the American Academy of Child and Adolescent Psychiatry (JAACAP), published by Elsevier, examines the prevalence of anxiety disorders and the impact of anxiety on disease-related outcomes for children and adolescents with CMCs.

The research team based in Australia and the Netherlands found the prevalence of anxiety disorders in youth with CMCs was higher than that in the general population. Anxiety may also be associated with adverse disease-related outcomes for children and adolescents with these conditions.

"The issue of 'mental-physical comorbidity' (i.e., meeting diagnostic criteria for least one mental illness and one physical disease) is critical, with the combination of anxiety disorders and physical disease appearing to be particularly prevalent among youth, said lead author Vanessa Cobham, PhD and clinical psychologist at the University of Queensland and Children's Health Queensland's Child and Youth Mental Health Service, Brisbane, Australia.

"Associated with significant implications, the combination of anxiety disorders and a physical disease presents the potential for worsened physical disease outcomes. Health professionals working with children and adolescents with chronic medical conditions should routinely screen for the presence of anxiety disorders in order to provide the best possible care to these youth."

The review based on 53 studies included the examination of prevalence of anxiety disorders and disease-related outcomes across seven different CMCs in children and adolescents with an average age of 18-years or younger.

Twenty-nine studies investigated the occurrence of anxiety disorders and found that more-than-half of the identified studies relied on only one informant (either the youth themselves or parent) in determining whether or not the youth met the criteria for an anxiety disorder. This was seen as the most significant limitation regarding the pervasiveness of an anxiety disorder.

While it is likely these studies underestimate the occurrence of anxiety disorders, the authors did find however that across all CMCs the anxiety prevalence rates were high: affecting approximately 20 percent to 50 percent of youth. In studies that included a healthy control group, rates of an anxiety disorder were substantially higher among patients with all CMCs. Across all CMCs, the rate of anxiety disorder was higher than the global prevalence rate of 6.5 percent as previously reported by Polanczyk and colleagues1.

The remaining 24 studies examined the impact of anxiety on disease-related outcomes. No studies were identified for disease-related outcomes for epilepsy or congenital heart disease, however the authors reported that anxiety was associated with:

poorer symptom control, school absenteeism, and higher rates of smoking in youth with asthma;
increased disease activity in youth with inflammatory bowel disease;
greater pain in youth with juvenile idiopathic arthritis; and
longer lengths of hospitalizations in youth with sickle cell disease presenting in vaso-occular crisis.

The most significant and common limitations in relation to the question of the impact of anxiety on disease-related outcomes were the cross-sectional design of most studies and the fact that almost all studies relied on one informant only in assessing both anxiety and disease-related outcomes.

The evidence for youth with diabetes was inconsistent, with some studies reporting a negative impact of anxiety on metabolic control and treatment adherence and other studies reporting a positive association between elevated anxiety and treatment adherence.

While evidence that anxiety is associated with adverse disease-related outcomes in these youth, more longitudinal research is needed to delineate the impact of anxiety on child outcomes, Dr. Cobham and her team concluded. It is recommended that health services routinely assess for anxiety disorders among youth with CMCs. Psychometrically validated anxiety questionnaires (both parent and youth versions) are likely to be a feasible means of screening for anxiety disorders.

Despite the traditional view that species do not exchange genes by hybridisation, recent studies show that gene flow between closely related species is more common than previously thought. A team of scientists from Uppsala University and Princeton University now reports how gene flow between two species of Darwin's finches has affected their beak morphology. The study is published today in Nature Ecology and Evolution.

Darwin's finches on the Galápagos Islands are an example of a rapid adaptive radiation in which 18 species have evolved from a common ancestral species within a period of 1-2 million years. Some of these species have only been separated for a few hundred thousand years or less.

Rosemary and Peter Grant of Princeton University, co-authors of the new study, studied populations of Darwin's finches on the small island of Daphne Major for 40 consecutive years and observed occasional hybridisation between two distinct species, the common cactus finch and the medium ground finch. The cactus finch is slightly larger than the medium ground finch, has a more pointed beak and is specialised to feed on cactus. The medium ground finch has a blunter beak and is specialised to feed on seeds.

"Over the years, we observed occasional hybridisation between these two species and noticed a convergence in beak shape. In particular, the beak of the common cactus finch became blunter and more similar to the beak of the medium ground finch," say Rosemary and Peter Grant. "We wondered whether this evolutionary change could be explained by gene flow between the two species."

"We have now addressed this question by sequencing groups of the two species from different time periods and with different beak morphology. We provide evidence of a substantial gene flow, in particular from the medium ground finch to the common cactus finch," explains Sangeet Lamichhaney, one of the shared first authors and currently Associate Professor at Kent State University.

"A surprising finding was that the observed gene flow was substantial on most autosomal chromosomes but negligible on the Z chromosome, one of the sex chromosomes," says Fan Han, Uppsala University, who analysed these data as part of her PhD thesis. "In birds, the sex chromosomes are ZZ in males and ZW in females, in contrast to mammals where males are XY and females are XX."

"This interesting result is in fact in excellent agreement with our field observation from the Galápagos," explain the Grants. "We noticed that most of the hybrids had a common cactus finch father and a medium ground finch mother. Furthermore, the hybrid females successfully bred with common cactus finch males and thereby transferred genes from the medium ground finch to the common cactus finch population. In contrast, male hybrids were smaller than common cactus finch males and could not compete successfully for high-quality territories and mates."

This mating pattern is explained by the fact that Darwin's finches are imprinted on the song of their fathers so that sons sing a song similar to their father's song and daughters prefer to mate with males that sing like their fathers. Furthermore, hybrid females receive their Z chromosome from their cactus finch father and their W chromosome from their ground finch mother. This explain why genes on the Z chromosome cannot flow from the medium ground finch to the cactus finch via these hybrid females, whereas genes in other parts of the genome can, because parents of the hybrid contribute equally.

"Our data show that the fitness of the hybrids between the two species is highly dependent on environmental conditions which affect food abundance," says Leif Andersson of Uppsala University and Texas A&M University. "That is, to what extent hybrids, with their combination of gene variants from both species, can successfully compete for food and territory. Therefore, the long-term outcome of the ongoing hybridisation between the two species will depend on environmental factors as well as competition."

"One scenario is that the two species will merge into a single species combining gene variants from the two species, but perhaps a more likely scenario is that they will continue to behave as two species and either continue to exchange genes occasionally or develop reproductive isolation if the hybrids at some point show reduced fitness compared with purebred progeny. The study contributes to our understanding of how biodiversity evolves," Andersson concludes.

(Boston)--Researchers have developed a computer algorithm based on Artificial Intelligence (AI) that can accurately predict the risk for and diagnose Alzheimer's disease using a combination of brain magnetic resonance imaging (MRI), testing to measure cognitive impairment, along with data on age and gender.

The AI strategy, based on a deep learning algorithm, is a type of machine learning framework. Machine learning is an AI application that enables a computer to learn from data and improve from experience. Alzheimer's disease is the primary cause of dementia worldwide. One in 10 people age 65 and older has Alzheimer's dementia. It is the sixth-leading cause of death in the United States.

"If computers can accurately detect debilitating conditions such as Alzheimer's disease using readily available data such as a brain MRI scan, then such technologies have a wide-reaching potential, especially in resource-limited settings," explained corresponding author Vijaya B. Kolachalama, PhD, assistant professor of medicine at Boston University School of Medicine (BUSM). "Not only can we accurately predict the risk of Alzheimer's disease but this algorithm can generate interpretable and intuitive visualizations of individual Alzheimer's disease risk en route to accurate diagnosis," said Kolachalama.

The researchers obtained access to raw MRI scans of the brain, demographics and clinical information of individuals with Alzheimer's disease and the ones with normal cognition from four different national cohorts. Using data from one of these cohorts, they developed a novel deep learning model to predict Alzheimer's disease risk. They then showed that their model could accurately predict the disease status on the other independent cohorts.

An international team of expert neurologists were then asked to perform the task of detecting Alzheimer's disease on the same set of cases. In this head-to-head comparison, the algorithm model performed slightly better than the average neurologist. They also showed that model-identified regions of high disease risk were highly aligned with autopsy reports of the brains on a few individuals who were deceased.

According to the researchers, this study has broad implications for expanding the use of neuroimaging data such as MRI scans to accurately detect the risk of Alzheimer's disease at the point of care. "If we have accurate tools to predict the risk of Alzheimer's disease (such as the one we developed), that are readily available and which can use routinely available data such as a brain MRI scan, then they have the potential to assist clinical practice, especially in memory clinics."

The researcher believe their methodology can be extended to other organs in the body and develop predictive models to diagnose other degenerative diseases.

As the coronavirus pandemic has swept across the U.S., in addition to tracking the number of COVID daily cases, there is a worldwide scientific community engaged in tracking the SARS-CoV-2 virus itself.

Efrem Lim leads a team at ASU that looks at how the virus may be spreading, mutating and adapting over time.

To trace the trail of the virus worldwide, Lim's team is using a new technology called next-generation sequencing at ASU's Genomics Facility, to rapidly read through all 30,000 chemical letters of the SARS-CoV-2 genetic code, called a genome.

Each sequence is deposited into a worldwide gene bank, run by a nonprofit scientific organization called GISAID. To date, over 16,000 SARS-CoV-2 sequences have been deposited GISAID's EpiCoVTM Database. The sequence data shows that SARS-CoV-2 originated a single source from Wuhan, China, while many of the first Arizona cases analyzed showed travel from Europe as the most likely source.

Now, using a pool of 382 nasal swab samples obtained from possible COVID-19 cases in Arizona, Lim's team has identified a SARS-CoV-2 mutation that had never been found before----where 81 of the letters have vanished, permanently deleted from the genome.

The study was published in the online version of the Journal of Virology.

Lim says as soon as he made the manuscript data available on a preprint server medRxiv, it has attracted worldwide interest from the scientific community, including the World Health Organization.

"One of the reasons why this mutation is of interest is because it mirrors a large deletion that arose in the 2003 SARS outbreak," said Lim, an assistant professor at ASU's Biodesign Institute. During the middle and late phases of the SARS epidemic, SARS-CoV accumulated mutations that attenuated the virus. Scientists believe that a weakened virus that causes less severe disease may have a selective advantage if it is able to spread efficiently through populations by people who are infected unknowingly.

Teasing apart what exactly this means is of profound interest to Lim and his colleagues. The ASU research team includes LaRinda A. Holland, Emily A. Kaelin, Rabia Maqsood, Bereket Estifanos, Lily I. Wu, Arvind Varsani, Rolf U. Halden, Brenda G. Hogue and Matthew Scotch.

The ASU virology team had been setup to perform research on seasonal flu viruses, but when the 3rd case of COVID-19 was found in an Arizona individual on January 26, 2020, they knew they had all technical and scientific prowess to rapidly pivot to examining the spread of SARS-CoV-2.

"This was the scientific opportunity of a lifetime for ASU to be able to contribute to understand how this virus is spreading in our community," said Lim. "As a team, we knew we could make a significant difference."

All the positive cases show that the SARS-CoV-2 viral genomes were different from each other, meaning they were independent from each other. This indicates that the new cases were not linked to the first Arizona case in January, but the result of recent travel from different locations.

In the case of the 81-base pair mutation, because it has never been found before in the GISAID database, it could also provide a clue into how the virus makes people sick. It could also form a new starting point for other scientists to develop antiviral drugs or formulate new vaccines.

SARS-CoV-2 makes accessory proteins that help it infect its human host, replicate and eventually spread from person to person. The genome deletion removes 27 protein building blocks, called amino acids, from the SARS-CoV-2 accessory protein ORF7a. The protein is very similar to the 2003 SARS-CoV immune antagonist ORF7a/X4.

The ASU team is now hard at work performing further experiments to understand the functional consequences of the viral mutation. The viral protein is thought to help SARS-CoV-2 evade human defenses, eventually killing the cell. This frees up the virus to infect other cells in a cascading chain reaction that can quickly cause the virus to make copies of itself throughout the body, eventually causing the serious COVID-19 symptoms 8-14 days after the initial infection.

Lim points out that only 16,000 SARS-CoV-2 genomes have been sequenced to date, which is less than 0.5% of the strains circulating. There are currently more than 3.5 million confirmed COVID-19 cases worldwide.

Lim's group has teamed up with TGen, UA and Northern Arizona University to continue tracking different genetic strains of the new coronavirus. Together, the newly formed Arizona COVID-19 Genomics Union (ACGU) hopes to use big data analysis and genetic mapping to give Arizona health care providers and public policy makers an edge in fighting the growing pandemic.

CORVALLIS, Ore. - Oregon State University College of Engineering researchers used a vacuum cleaner and the personalities of three of the Seven Dwarfs from Snow White to demonstrate that people can correctly infer a robot's personality solely by how it moves.

Unexpectedly, study participants also discerned intelligence from robot motion behaviors, suggesting people might trust an autonomous system more or less depending on their observations of its movements.

The findings are noteworthy because, much like the importance of personality in people's interactions, robot personality can influence engagement and trust.

The study was published by the Association for Computing Machinery/Institute of Electrical and Electronics Engineering's International Conference on Human-Robot Interaction.

Researchers in the lab of OSU assistant professor of computer science Heather Knight equipped a Neato Botvac vacuum cleaning robot with movement patterns inspired by the personalities of Happy, Sleepy and Grumpy.

Human participants rated the politeness, friendliness and intelligence of each robot motion demonstration after a series of trials that illustrated each of the motion personalities, without being informed of the robot's intended personalities.

"We implemented an expressive autonomous motion generation system that mapped each personality the robots motion features, such as path shape, acceleration and velocity characteristics, and whether they moved toward or away from the participant," Knight said. "The Happy robot sought people out with smooth motions at moderate speed. The Sleepy robot also sought people out, but with delays and slower accelerations. The Grumpy robot avoided people while using erratic motions and a range of velocities. Those simple variations told the people a lot."

True to form, study participants rated Grumpy as the least polite and least friendly, whereas Happy upheld reputation by being rated the friendliest and smartest. Happy and Sleepy were together deemed most polite, though their rating was just above neutral.

"Participants were able to distinguish the motion-based personas, which bodes well for the integration of robot personality into simple robots" Knight said. "In future work, we hope to extend this work to the other four Dwarfs and study how personality could positively impact the specific tasks a robot is taking on around people."

Rutgers Robert Wood Johnson Medical School student Paul Lavadera expected his career would put him on the front lines of dealing with medical emergencies.

But he never could have imagined he'd be graduating during the biggest global pandemic in a century when he joined forces two years ago with Tracey Shors, Distinguished Professor of Neuroscience and Psychology, on a study to find out whether aerobic exercise and meditation would reduce stress and improve the quality of life for medical students like him.

Now Lavadera, who begins a four-year emergency medicine residency on June 29 at a COVID-19 only hospital in Brooklyn and Shors, who thinks she may have battled a case of the coronavirus, are using the stress-reducing technique taught to RWJMS medical school students to help them each deal with the anxiety and uncertainty left in the path of the crisis.

"I am isolating alone in my apartment and keeping myself up to date on the evolving guidelines on treatments and recommendations regarding COVID19, but I'm making a conscious decision to avoid sensational and minute-by-minute news," says Lavadera who will split his time between two Brooklyn hospitals - Kings County Hospital in Flatbush and SUNY Downstate Medical Center, one of only three New York hospitals treating COVID-19 only patients. "I am working out, mediating and doing the training program that I helped to promote to medical school students. I think it keeps me afloat and helps to keep my stress level down."

The new Rutgers study in the Journal of Alternative and Complementary Medicine, Lavadera coauthored with Shors and doctoral student Emma Millon, documents the effectiveness of the technique that helped them both through this difficult time. The researchers found that meditation combined with aerobic exercise reduces stress and rumination while enhancing the quality of life for medical students.

Over an eight-week period first and second-year medical school students participated in the intervention called MAP Train My Brain™, twice a week, which included 30 minutes of meditation followed by 30 minutes of aerobic exercise compared to a control group of student who did neither.

Shors - who developed the MAP (mental and physical) Training for those with depression, trauma and stress-related symptoms - has studied the effects of this training on different groups, including women who have been sexually assaulted and most recently women living with HIV, a study which has not yet been published.

When Shors began the study on medical school students with Lavadera she thought she understood how stressful treating patients could be for physicians. But she gained deeper insight during her recent illness.

For about six weeks from late February to early April, Shors suffered with coronavirus symptoms at home: trouble breathing, a persistent cough, and debilitating fatigue. She went to packed emergency departments twice, got a chest x-ray that showed no pneumonia and was sent home to isolate without getting a COVID-19 test because she didn't have a fever.

Shors remembers the doctors and nurses. "Behind their masks, I could see in their eyes the stress and anxiety that they are feeling, but I also experienced the professionalism and compassion that they bring to each person coming in for help," said Shors, vice chair/director of Graduate Studies in the department of psychology Center for Collaborative Neuroscience in the School of Arts and Sciences at Rutgers University-New Brunswick.

The study, which researchers believe is the first to document positive outcomes with such an intervention on medical students, found that the students doing the MAP Training experienced significantly less stress and were approximately 20 percent less likely to ruminate with depressive and brooding thoughts, when compared to medical students in the control group who did not participate in the program.

Most importantly, researchers say, is that those involved in the study said the training improved their quality of life, with 84 percent of the medical school students saying that they would recommend MAP Train My BrainTM to future patients as a way to alleviate anxiety and stress and improve overall health.

Shors and Lavadera say while the aim of the study was to provide a program for medical school students that would keep them physically and mentally healthy, they also hoped that it would be a program that they would want to recommend to future patients.

As the uncertainty of what lies ahead with the global COVID-19 pandemic continues, both Shors, who at the height of what she believes was her bout with coronavirus, worried that she would have to be hooked to a ventilator, and Lavadera, who has been trying to stay away from the daily drumbeat of coronavirus news before he has to deal with it firsthand, says this meditation and aerobic exercise program allows them to do it at home, alone.

"It is always important to reduce stress but especially important and difficult to do during this traumatic time," says Shors. "We are living with the threat of illness and even death for ourselves and our loved ones. There is nothing more stressful than that."